Aberrant glycosylation in the human trabecular meshwork.

Aberrant glycosylation in the human trabecular meshwork.
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DOI:
10.1002/prca.201300031
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发表时间:
2014-04
影响因子:
2
通讯作者:
Bhattacharya, Sanjoy K.
Bhattacharya, Sanjoy K.
中科院分区:
生物学3区
文献类型:
--
作者:
Sienkiewicz, Adam E.;Rosenberg, Brandon N.;Edwards, Genea;Carreon, Teresia A.;Bhattacharya, Sanjoy K.

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To determine the difference in protein glycosylation and glycosylation enzyme levels between glaucomatous and control trabecular meshwork (TM). Glaucomatous and normal donor (n=12 each) TM tissues, Lectin-fluorescence, fluorophore assisted carbohydrate analyses, and quantitative mass spectrometry were used to determine the glycosylation levels. Primary TM cells and glycosylation inhibitors were used to determine their effect on cell shape and motility. In contrast to elevated levels of glycoproteins determined by lectin-fluorescence, simultaneous hyper and hypo-glycosylation in glaucomatous trabecular meshwork was revealed by fluorophore assisted carbohydrate analyses. Analyses of enzymes showed elevation of Beta-glycosidase 1 and decrease in Galactosyltransferase family 6 domain containing protein 1 in the glaucomatous trabecular meshwork. Quantitative mass spectrometry identified select protein level changes between glaucomatous and normal trabecular meshwork. Primary trabecular meshwork cells were treated with inhibitors to elicit hypo-glycosylation, which affected cell shape, motility, and fluorescent tracer transport across a layer of trabecular meshwork cells. Global protein glycosylation is aberrant in glaucomatous trabecular meshwork compared to controls. The results presented here suggest that the alteration in global TM protein glycosylation encompassing cellular and extracellular matrix proteins contributes to glaucoma pathology likely mediated through changes in properties of TM cells.
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